Optimization of histamine and histamine H₄ receptor agonist-induced allergic conjunctivitis model in guinea pigs

<p>In this study, we verified the reproducibility of an animal model in the previous report and made improvements in test methods focusing on a guinea pig model of histamine and histamine H4 receptor agonist-induced allergic conjunctivitis. </p><p>Histamine or 4MeHA was instilled into the conjunctival sacs of animals to induce conjunctivitis symptoms, and the optimal dose level of histamine and 4MeHA for evaluation was determined. Furthermore, the drug efficacy evaluation was conducted using a commercially available antihistamine drug or histamine H4 receptor antagonist to judge the suitability of the improved model. The evaluation items commonly used in animal models of conjunctivitis, i.e., scoring of conjunctivitis, observations of scratching behaviors, and measurements of conjunctival vascular permeability, were selected. The Draize scale and McDonald-Shadduck scoring system were used for the scoring of conjunctivitis.</p><p>In the histamine model, the dose level of histamine needed to be increased in order to use the existing model, but allergic-like symptoms were induced very easily and stably, and it was possible to evaluate the efficacy of antihistamines. In the 4MeHA model, conjunctival and iris hyperemia was confirmed and it was specifically suppressed by histamine H4 receptor antagonist. However, edema was not observed, and increased vascular permeability and increased scratching behavior could not be confirmed. Although it is not a model that comprehensively reflects the symptoms of allergic conjunctivitis, it is possible that this model can be used as a simple screening model.</p>